Multi-Institutional Phase II Study of IMC-A12, a Recombinant Human IgG1 Monoclonal Antibody Directed at the Type I Insulin-Like Growth Factor Receptor IGF1R, in Adrenocortical Carcinoma: IMC-A12 With Mitotane vs Mitotane Alone
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 20
- 试验地点
- 8
- 主要终点
- Progression-free Survival Rate at 6 Weeks
研究概览
简要总结
This randomized phase II trial is studying mitotane and IMC-A12 to see how well they work compared with mitotane alone in treating patients with recurrent, metastatic, or primary adrenocortical cancer that cannot be removed by surgery. Drugs used in chemotherapy, such as mitotane, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as IMC-A12, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether mitotane is more effective with or without monoclonal antibody IMC-A12 in treating adrenocortical cancer.
详细描述
PRIMARY OBJECTIVES:
I. Compare the progression-free survival (PFS) rate in patients with recurrent, metastatic, or primary unresectable adrenocortical carcinoma treated with mitotane with vs without anti-IGF-1R recombinant monoclonal antibody IMC-A12 (IMC-A12).
SECONDARY OBJECTIVES:
I. Compare the response rates in these patients using Response Evaluation Criteria in Solid Tumor (RECIST) criteria.
II. Compare the change in tumor size from baseline to 12 weeks in these patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed adrenocortical carcinoma
- •Documented unresectable recurrent, unresectable advanced, or metastatic disease
- •At least 1 lesion that can be accurately measured by RECIST criteria as ≥ 20 mm by conventional radiologic techniques or as ≥ 10 mm by spiral CT scan or MRI
- •Patients with disease in an irradiated field as the only site of measurable disease allowed provided there has been a clear progression of the lesion
- •No tumors potentially resectable by surgical excision alone
- •No known or suspected leptomeningeal disease or brain metastases
- •ECOG performance status 0-2
- •Life expectancy ≥ 12 weeks
- •ANC ≥ 1,500/mm^3
- •Platelet count ≥ 100,000/mm^3
- •Hemoglobin ≥ 9 g/dL (transfusion allowed)
- •Serum creatinine ≤ 1.5 times upper limit of normal (ULN) OR calculated creatinine clearance ≥ 60 mL/min
- •AST or ALT ≤ 3 times ULN
- •Total bilirubin ≤ 1.5 times ULN
- •HbA1c < 8 within the past 4 weeks
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception during and for 3 months after completion of study therapy
- •Able to take oral medications
- •No poor gastrointestinal absorption
- •Patients with diabetes mellitus are eligible provided they meet all of the following criteria:
- •Blood glucose is normal (random glucose ≤ 150 mg/dL)
- •HgbA1c ≤ 8 within the past 4 weeks
- •On a stable dietary or therapeutic regimen for the past 2 months
- •No active uncontrolled infection
- •No severe disease or condition that, in the judgement of the investigator, would make the patient inappropriate for study participation, including, but not limited to:
- •Bleeding diathesis
- •Uncontrolled chronic kidney or liver disease
- •Uncontrolled diabetes
- •History of cardiac history
- •Myocardial infarction within the past 6 months
- •Congestive heart failure
- •Unstable angina pectoris
- •Cardiac arrhythmia
- •Uncontrolled hypertension
- •No current malignancy or previous malignancy with a disease-free interval of < 2 years at the time of diagnosis
- •Patients with adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or skin, or stage A low-grade prostate cancer are eligible
- •No known hypersensitivity to monoclonal antibody therapy or mitotane
- •No known HIV or hepatitis B or C infection
- •No serious medical or psychiatric disorder that would interfere with patient safety or informed consent
- •All significant toxic effects of prior surgery resolved to ≤ grade 1 according to NCI CTCAE v. 3.0 criteria
- •Mitotane for < 8 weeks prior to study entry AND tolerated it well
- •No prior IGFR-directed therapy
- •No prior systemic antitumor therapy (cytotoxic chemotherapy, biologic, immunotherapy, or targeted therapy)
- •Prior incomplete surgical resections or radiofrequency ablation or radiotherapy will not be considered as prior therapy provided measurable sites of disease remain
- •Prior adjuvant chemotherapy or mitotane will not be considered as prior antitumor therapy unless it was completed < 6 months before study enrollment
- •No prior radiotherapy to > 20% of bone marrow
- •More than 4 weeks since prior and no concurrent radiotherapy
- •Radiotherapy for palliation of symptoms related to metastases is permitted provided that it is > 4 weeks from study initiation, and does not involve target/measureable lesions that are followed for drug treatment response evaluation
- •No concurrent mitotane ≥ 8 weeks prior to study
- 另有 2 项未显示
排除标准
- 未提供
研究组 & 干预措施
Arm II (Mitotane + IMC-A12)
Patients receive mitotane as in arm I and anti-IGF-1R recombinant monoclonal antibody IMC-A12 IV over 1 hour once every 2 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: IMC-A12 (Biological)
Arm II (Mitotane + IMC-A12)
Patients receive mitotane as in arm I and anti-IGF-1R recombinant monoclonal antibody IMC-A12 IV over 1 hour once every 2 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: mitotane (Drug)
结局指标
主要结局
Progression-free Survival Rate at 6 Weeks
时间窗: 6 weeks
Progression-free survival rates were estimated at 6, 12, and 18 weeks by the Kaplan-Meier method. At a given time point, this outcome is defined as the proportion of subjects who had not progressed or died. Disease progression is defined according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0). Progression is characterized by a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Progression-free Survival Rate at 12 Weeks
时间窗: 12 weeks
Progression-free survival rates were estimated at 6, 12, and 18 weeks by the Kaplan-Meier method. At a given time point, this outcome is defined as the proportion of subjects who had not progressed or died. Disease progression is defined according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0). Progression is characterized by a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Progression-free Survival Rate at 18 Weeks
时间窗: 18 weeks
Progression-free survival rates were estimated at 6, 12, and 18 weeks by the Kaplan-Meier method. At a given time point, this outcome is defined as the proportion of subjects who had not progressed or died. Disease progression is defined according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0). Progression is characterized by a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
次要结局
- Number of Patients Exhibiting Decrease in Tumor Size at 12 Weeks(12 weeks)
- Number of Patients Exhibiting Decrease in Tumor Size at 18 Weeks(18 weeks)
- Number of Patients Exhibiting Decrease in Tumor Size at 48 Weeks(48 weeks)
- Response at 12 Weeks(12 weeks)
- Response at 18 Weeks(18 weeks)
- Response at 48 Weeks(48 weeks)
- Number of Patients Exhibiting Decrease in Tumor Size at 6 Weeks(6 weeks)
- Best Response Rates(Up to 6 months)
- Response at 6 Weeks(6 weeks)